Figure 1. Regulation of lipid metabolism by hepatic AMPK.

Activation of AMPK leads to the inhibition of cholesterol synthesis by phosphorylation of HMG-CoA reductase. By inhibiting ACC and activating MCD, AMPK increases fatty acid oxidation via the regulation of levels of malonyl-CoA, which is both a critical precursor for biosynthesis of fatty acids and a potent inhibitor of CPT-1, the enzyme that controls the transfer of long-chain fatty acyl-CoA into the mitochondria. AMPK inhibits also GPAT, the first committed enzyme in glycerolipid synthesis. The net resulting effect of AMPK activation is to inhibit energy-consuming lipogenic pathways (fatty acid, triglyceride and sterol synthesis) in favour of fatty acid oxidation. FA-CoA: fatty acyl-CoA.